ACTA ENDOCRINOLOGICA (BUC)

The International Journal of Romanian Society of Endocrinology / Registered in 1938

in Web of Science Master Journal List

Acta Endocrinologica(Bucharest) is live in PubMed Central

Journal Impact Factor - click here.

January - March 2005, Volume 1, Issue 1
General Endocrinology


Galoiu SA, Kertesz G, Somma C, Coculescu M, Brue T

Clinical expression of big-big prolactin and influence of macroprolactinemia upon immunodiagnostic tests

Acta Endo (Buc) 2005, 1 (1): 31-41
doi: 10.4183/aeb.2005.31

In some humans, the big and big-big prolactin variants represent the majority of circulating prolactin, considered to be without biological activity. Aims: to establish the clinical expression of macroprolactinemia and the interference with immunodiagnostic tests\r\nin a randomized group of 84 consecutive patients with hyperprolactinemia. IRMA and electrochemiluminescence (Elecsys) were used for PRL assay; gel filtration chromatography (GFC) and protein A precipitation test were used to reveal macroprolactinemia. Results: Macroprolactinemia was found in 16 out of 84 patients (group A), 62 patients had hyperprolactinemia of other causes (group B) and 6 had normal PRL levels and normal GFC (group C). Of 16 patients with macroprolactinemia, 6 showed normal PRL with IRMA and hyperprolactinemia with Elecsys. The difference between the two methods used (&#8710; = PRL determined by Elecsys, -PRL determined by IRMA) correlated with big big PRL level determined by GFC with Elecsys in all patients. The strongest correlation was found in patients with macroprolactinemia (group A, r=0.82, p<0.01) as compared with group B, without macroprolactinemia (r=0.39, p<0.01). Menstrual disorders were expressed, but less frequent in group A versus B (3/15 vs. 28/56, p=0.04), and the appearance of galactorrhea and infertility were not statistically different. Conclusions: In these patients, macroprolactinemia had clinical expression, but weaker than in true hyperprolactinemic patients. It determines high apparent variability of serum PRL level in current commercial assays.

Keywords: macroprolactinemia, big-big prolactin, immunoassay, hyperprolactinemia

Correspondence: Simona Galoiu, Department of Endocrinology, ?Carol Davila? University of Medicine and Pharmacy, Bucharest, Romania, e-mail: simonagaloiu@yahoo.com

References:

1. Ben Jonathan N, Liby K, McFarland M, Zinger M. Prolactin as an autocrine/paracrine growth factor in human cancer. Trends Endocrinol Metab 2002; 13(6):245-250. [CrossRef]
2. Jackson RD, Wortsman J, Malarkey WB. Characterization of a large molecular weight prolactin in women with idiopathic hyperprolactinemia and normal menses. J Clin Endocrinol Metab 1985; 61(2):258-264. [CrossRef]
3. Kline JB, Clevenger CV. Identification and characterization of the prolactin-binding protein in human serum and milk. J Biol Chem 2001; 276(27):24760-24766. [CrossRef]
4. Piketty M-L, Lancelin F, Poirier-Begue E, Coussieu C. Le dosage de la prolactine et ses pieges. Reproduction Humaine et Hormones 2002; XV(1-2):7-16.
5. Hattori N, Ishihara T, Ikekubo K, Moridera K, Hino M, Kurahachi H. Autoantibody to human prolactin in patients with idiopathic hyperprolactinemia. J Clin Endocrinol Metab 1992; 75(5):1226- 1229. [CrossRef]
6. Bonhoff A, Vuille JC, Gomez F, Gellersen B. Identification of macroprolactin in a patient with asymptomatic hyperprolactinemia as a stable PRL-IgG complex. Exp Clin Endocrinol Diabetes 1995; 103(4):252-255. [CrossRef]
7. Cacavo B, Leite V, Santos MA, Arranhado E, Sobrinho LG. Some forms of big big prolactin behave as a complex of monomeric prolactin with an immunoglobulin G in patients with macroprolactinemia or prolactinoma. J Clin Endocrinol Metab 1995; 80(8):2342-234 [CrossRef]
8. De Schepper J, Schiettecatte J, Velkeniers B, Blumenfeld Z, Shteinberg M, Devroey P et al. Clinical and biological characterization of macroprolactinemia with and without prolactin-IgG complexes. Eur J Endocrinol 2003; 149(3):201-207. [CrossRef]
9. Hattori N. The frequency of macroprolactinemia in pregnant women and the heterogeneity of its etiologies. J Clin Endocrinol Metab 1996; 81(2):586-590. [CrossRef]
10. Cavaco B, Prazeres S, Santos MA, Sobrinho LG, Leite V. Hyperprolactinemia due to big big prolactin is differently detected by commercially available immunoassays. J Endocrinol Invest 1999; 22(3):203-208.
11. Ahlquist JA, Fahie-Wilson MN, Cameron J. Variable detection of macroprolactin: a cause of apparent change in serum prolactin levels. Clin Endocrinol (Oxf) 1998; 48(1):123-124. [CrossRef]
12. Ahlquist JA, Fahie-Wilson MN, Cameron J. Variable detection of macroprolactin: a cause of apparent change in serum prolactin levels. Clin Endocrinol (Oxf) 1998; 48(1):123-124. [CrossRef]
13. Vallette-Kasic S, Morange-Ramos I, Selim A, Gunz G, Morange S, Enjalbert A et al. Macroprolactinemia revisited: a study on 106 patients. J Clin Endocrinol Metab 2002; 87(2):581-588. [CrossRef]
14. Fahie-Wilson MN, Soule SG. Macroprolactinaemia: contribution to hyperprolactinaemia in a district general hospital and evaluation of a screening test based on precipitation with polyethylene glycol. Ann Clin Biochem 1997; 34 ( Pt 3):252-258.
15. Garcia ML, Diez HA, Ciriza de los RC, Delgado GM, Orejas GA, Fernandez Erales AL et al. Macroprolactin as etiology of hyperprolactinemia. Method for detection and clinical characterization of the entity in 39 patients. Rev Clin Esp 2003; 203(10):459-464
16. Hauache OM, Rocha AJ, Maia AC, Maciel RM, Vieira JG. Screening for macroprolactinaemia and pituitary imaging studies. Clin Endocrinol (Oxf) 2002; 57(3):327-331. [CrossRef]
17. Leanos A, Pascoe D, Fraga A, Blanco-Favela F. Anti-prolactin autoantibodies in systemic lupus erythematosus patients with associated hyperprolactinemia. Lupus 1998; 7(6):398-403. [CrossRef]
18. Pacilio M, Migliaresi S, Meli R, Ambrosone L, Bigliardo B, Di Carlo R. Elevated bioactive prolactin levels in systemic lupus erythematosus?association with disease activity. J Rheumatol 2001; 28(10):2216-2221.
19. Rogol AD, Eastman RC, Manolio T, Rosen SW. Unusual heterogeneity of circulating prolactin in an acromegalic. J Endocrinol Invest 1981; 4(2):221-22
20. Andersen AN, Pedersen H, Larsen JF, Djursing H. Preserved prolactin fluctuations and response to metoclopramide in ovulatory, infertile, hyperprolactinemic women. Acta Obstet Gynecol Scand 1984; 63(2):141-144. [CrossRef]
21. Andino NA, Bidot C, Valdes M, Machado AJ. Chromatographic pattern of circulating prolactin in ovulatory hyperprolactinemia. Fertil Steril 1985; 44(5):600-605.
22. Colon JM, Ginsburg F, Schmidt CL, Weiss G. Hyperprolactinemia in clinically asymptomatic, fertile men: report of two cases. Obstet Gynecol 1989; 74(3 Pt 2):510-513.
23. Guay AT, Sabharwal P, Varma S, Malarkey WB. Delayed diagnosis of psychological erectile dysfunction because of the presence of macroprolactinemia. J Clin Endocrinol Metab 1996; 81(7):2512-2514. [CrossRef]
24. Guitelman M, Colombani-Vidal ME, Zylbersztein CC, Fiszlejder L, Zeller M, Levalle O et al. Hyperprolactinemia in asymptomatic patients is related to high molecular weight posttranslational variants or glycosylated forms. Pituitary 2002; 5(4):255-260. [CrossRef]
25. Vallette-Kasic S, Morange-Ramos I, Selim A, Gunz G, Morange S, Enjalbert A et al. Macroprolactinemia revisited: a study on 106 patients. J Clin Endocrinol Metab 2002; 87(2):581-588. [CrossRef]
26. Suliman AM, Smith TP, Gibney J, McKenna TJ. Frequent misdiagnosis and mismanagement of hyperprolactinemic patients before the introduction of macroprolactin screening: application of a new strict laboratory definition of macroprolactinemia. Clin Chem 20 [CrossRef]
27. Olukoga AO, Kane JW. Macroprolactinaemia: validation and application of the polyethylene glycol precipitation test and clinical characterization of the condition. Clin Endocrinol (Oxf) 1999; 51(1):119-126. [CrossRef]
28. Cavaco B, Leite V, Santos MA, Arranhado E, Sobrinho LG. Some forms of big big prolactin behave as a complex of monomeric prolactin with an immunoglobulin G in patients with macroprolactinemia or prolactinoma. J Clin Endocrinol Metab 1995; 80(8):2342-234 [CrossRef]
29. Strachan MW, Teoh WL, Don-Wauchope AC, Seth J, Stoddart M, Beckett GJ. Clinical and radiological features of patients with macroprolactinaemia. Clin Endocrinol (Oxf) 2003; 59(3):339- 346. [CrossRef]
30. Vallette-Kasic S, Morange-Ramos I, Selim A, Gunz G, Morange S, Enjalbert A et al. Macroprolactinemia revisited: a study on 106 patients. J Clin Endocrinol Metab 2002; 87(2):581-588. [CrossRef]
31. Pacilio M, Migliaresi S, Meli R, Ambrosone L, Bigliardo B, Di Carlo R. Elevated bioactive prolactin levels in systemic lupus erythematosus?association with disease activity. J Rheumatol 2001; 28(10):2216-2221.
32. Jackson RD, Wortsman J, Malarkey WB. Characterization of a large molecular weight prolactin in women with idiopathic hyperprolactinemia and normal menses. J Clin Endocrinol Metab 1985; 61(2):258-264. [CrossRef]
33. Andino NA, Bidot C, Valdes M, Machado AJ. Chromatographic pattern of circulating prolactin in ovulatory hyperprolactinemia. Fertil Steril 1985; 44(5):600-605.
34. Fraser IS, Lun ZG, Zhou JP, Herington AC, McCarron G, Caterson I et al. Detailed assessment of big big prolactin in women with hyperprolactinemia and normal ovarian function. J Clin Endocrinol Metab 1989; 69(3):585-592. [CrossRef]
35. Hattori N, Ikekubo K, Ishihara T, Moridera K, Hino M, Kurahachi H. A normal ovulatory woman with hyperprolactinemia: presence of anti-prolactin autoantibody and the regulation of prolactin secretion. Acta Endocrinol (Copenh) 1992; 126(6):497-500.
36. Andino NA, Bidot C, Valdes M, Machado AJ. Chromatographic pattern of circulating prolactin in ovulatory hyperprolactinemia. Fertil Steril 1985; 44(5):600-605.
37. Whittaker PG, Wilcox T, Lind T. Maintained fertility in a patient with hyperprolactinemia due to big, big prolactin. J Clin Endocrinol Metab 1981; 53(4):863-866. [CrossRef]
38. Jackson RD, Wortsman J, Malarkey WB. Characterization of a large molecular weight prolactin in women with idiopathic hyperprolactinemia and normal menses. J Clin Endocrinol Metab 1985; 61(2):258-264. [CrossRef]
39. Colon JM, Ginsburg F, Schmidt CL, Weiss G. Hyperprolactinemia in clinically asymptomatic, fertile men: report of two cases. Obstet Gynecol 1989; 74(3 Pt 2):510-513.
40. Hattori N, Ikekubo K, Ishihara T, Moridera K, Hino M, Kurahachi H. A normal ovulatory woman with hyperprolactinemia: presence of anti-prolactin autoantibody and the regulation of prolactin secretion. Acta Endocrinol (Copenh) 1992; 126(6):497-500.
41. Leite V, Cosby H, Sobrinho LG, Fresnoza MA, Santos MA, Friesen HG. Characterization of big, big prolactin in patients with hyperprolactinaemia. Clin Endocrinol (Oxf) 1992; 37(4):365-372. [CrossRef]
42. Leslie H, Courtney CH, Bell PM, Hadden DR, McCance DR, Ellis PK et al. Laboratory and clinical experience in 55 patients with macroprolactinemia identified by a simple polyethylene glycol precipitation method. J Clin Endocrinol Metab 2001; 86(6):2743-27 [CrossRef]
43. Vallette-Kasic S, Morange-Ramos I, Selim A, Gunz G, Morange S, Enjalbert A et al. Macroprolactinemia revisited: a study on 106 patients. J Clin Endocrinol Metab 2002; 87(2):581-588. [CrossRef]
44. Suliman AM, Smith TP, Gibney J, McKenna TJ. Frequent misdiagnosis and mismanagement of hyperprolactinemic patients before the introduction of macroprolactin screening: application of a new strict laboratory definition of macroprolactinemia. Clin Chem 20 [CrossRef]
45. De Schepper J, Schiettecatte J, Velkeniers B, Blumenfeld Z, Shteinberg M, Devroey P et al. Clinical and biological characterization of macroprolactinemia with and without prolactin-IgG complexes. Eur J Endocrinol 2003; 149(3):201-207. [CrossRef]
46. Leite V, Cosby H, Sobrinho LG, Fresnoza MA, Santos MA, Friesen HG. Characterization of big, big prolactin in patients with hyperprolactinaemia. Clin Endocrinol (Oxf) 1992; 37(4):365-372. [CrossRef]
47. Leite V, Cosby H, Sobrinho LG, Fresnoza MA, Santos MA, Friesen HG. Characterization of big, big prolactin in patients with hyperprolactinaemia. Clin Endocrinol (Oxf) 1992; 37(4):365-372. [CrossRef]
48. Hattori N, Inagaki C. Anti-prolactin (PRL) autoantibodies cause asymptomatic hyperprolactinemia: bioassay and clearance studies of PRL-immunoglobulin G complex. J Clin Endocrinol Metab 1997; 82(9):3107-3110. [CrossRef]
49. Hattori N, Inagaki C. Anti-prolactin (PRL) autoantibodies cause asymptomatic hyperprolactinemia: bioassay and clearance studies of PRL-immunoglobulin G complex. J Clin Endocrinol Metab 1997; 82(9):3107-3110. [CrossRef]
50. Jackson RD, Wortsman J, Malarkey WB. Macroprolactinemia presenting like a pituitary tumor. Am J Med 1985; 78(2):346-350. [CrossRef]
51. Mounier C, Trouillas J, Claustrat B, Duthel R, Estour B. Macroprolactinaemia associated with prolactin adenoma. Hum Reprod 2003; 18(4):853-857. [CrossRef]
52. John R, McDowell IF, Scanlon MF, Ellis AR. Macroprolactin reactivities in prolactin assays: an issue for clinical laboratories and equipment manufacturers. Clin Chem 2000; 46(6 Pt 1):884-885.
53. Gilson G, Schmit P, Thix J, Hoffman JP, Humbel RL. Prolactin results for samples containing macroprolactin are method and sample dependent. Clin Chem 2001; 47(2):331-333.
54. Gilson G, Schmit P, Thix J, Hoffman JP, Humbel RL. Prolactin results for samples containing macroprolactin are method and sample dependent. Clin Chem 2001; 47(2):331-333.